BACKGROUND: Evidence suggests that brain iron deficiency at any time in life may disrupt metabolic processes and subsequently change cognitive and behavioral functioning. Women of reproductive age are among those most vulnerable to iron deficiency and may be at high risk for cognitive alterations due to iron deficiency. OBJECTIVE: We aimed to examine the relation between iron status and cognitive abilities in young women. DESIGN: A blinded, placebo-controlled, stratified intervention study was conducted in women aged 18-35 y of varied iron status who were randomly assigned to receive iron supplements or a placebo. Cognition was assessed by using 8 cognitive performance tasks (from Detterman's Cognitive Abilities Test) at baseline (n = 149) and after 16 wk of treatment (n = 113). RESULTS: At baseline, the iron-sufficient women (n = 42) performed better on cognitive tasks (P = 0.011) and completed them faster (P = 0.038) than did the women with iron deficiency anemia (n = 34). Factors representing performance accuracy and the time needed to complete the tasks by the iron-deficient but nonanemic women (n = 73) were intermediate between the 2 extremes of iron status. After treatment, a significant improvement in serum ferritin was associated with a 5-7-fold improvement in cognitive performance, whereas a significant improvement in hemoglobin was related to improved speed in completing the cognitive tasks. CONCLUSIONS: Iron status is a significant factor in cognitive performance in women of reproductive age. Severity of anemia primarily affects processing speed, and severity of iron deficiency affects accuracy of cognitive function over a broad range of tasks. Thus, the effects of iron deficiency on cognition are not limited to the developing brain.

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Nonhematologic manifestations of ID include reduced physical endurance, an impaired immune response, difficulty in regulating temperature, changes in energy metabolism, decreased cognitive performance, and behavioral disturbances (2–4). Over the past 30 y, a large effort has focused on understanding the relation between ID and development or behavior in infants and young children (4–8). As a result, we have strong evidence that IDA is associated with poorer performance on developmental ratings in infants and with lower scores on cognitive function tests and educational achievement tests in children. In adolescents, ID has been shown to impair cognitive abilities even in the absence of overt anemia (9).

Whereas data on the relation between iron status and cognition is mounting in both infants and children, a gap exists in our understanding of this same relation in adults. The large number of studies conducted in infants has led many to assume that ID disrupts brain functioning only during development (10). However, new evidence from animal models and in humans with restless leg syndrome (RLS) suggests that brain ID at any time in life is likely to disrupt metabolic processes and to be followed by changes in cognitive and behavioral functioning (4).

Reports have been published of cognitive improvement in adult renal dialysis patients who are receiving both erythropoietin and iron supplementation as part of treatment protocols (11–13), as well as in elderly whose iron nutritional status has improved (14). Recently, we reported a relation between iron status and cognitive abilities in poor South African mothers during the first postpartum year (15). Whereas these studies all point to a relation between iron status and cognition, the numerous confounding variables in each of them make the findings difficult to assess. Therefore, we undertook a more thorough investigation of the relation between iron status and cognition in women of reproductive age by conducting a blinded, placebo-controlled, intervention study. The overall aim of the study was to examine the effects of ID and IDA on cognitive and emotional performance in young women. Here we report the results of the cognitive tasks. The primary outcomes of the study were the relation between iron status and cognition and that between changes in iron status and changes in cognition. We also wanted to examine whether different facets of cognition were differentially affected by iron status or a change in iron status. Given estimates that up to 50% of women in the world are iron deficient, a documented relation between iron status and cognitive abilities could provide a basis for interventions that would be relevant to the psychological functioning of a significant proportion of the world’s population.